An in-vitro model to study device-induced thrombosis and embolism: evaluation of the efficacy of tirofiban, aspirin, and dipyridamole

A bovine in-vitro model was developed to investigate device-induced thromboembolism (TE) and its pharmacological intervention, using a stent as a prototype device. Emboli were assessed continuously using a light-scattering microemboli detector (LSMD). Thrombus on the stent was assessed gravimetrically at the end of the experiment. The contribution of the stent as the predominant source of detectable thromboemboli in this model was verified by placing LSMD probes upstream and downstream of the stent. The effectiveness of ethylenedinitrilo-tetraacetic-acid (EDTA) and three anti-thrombogenic agents (aspirin, dipyridamole, and tirofiban) for mitigating device-induced TE was also assessed. The results show that 1) the model has potential to study device-induced TE and the efficacy of possible interventional strategies, 2) the LSMD is capable of continuous, non-invasive, real-time assessment of embolism, 3) the assessment of embolization may constitute an important part of evaluating hemocompatibility, 4) tirofiban is effective in reducing both stent-induced thrombosis and embolism above certain concentrations.     

Application of Poisson kriging to the mapping of cholera and dysentery incidence in an endemic area of Bangladesh

Background  

Disease maps can serve to display incidence rates geographically, to inform on public health provision about the success or failure of interventions, and to make hypothesis or to provide evidences concerning disease etiology. Poisson kriging was recently introduced to filter the noise attached to rates recorded over sparsely populated administrative units. Its benefit over simple population-weighted averages and empirical Bayesian smoothers was demonstrated by simulation studies using county-level cancer mortality rates. This paper presents the first application of Poisson kriging to the spatial interpolation of local disease rates, resulting in continuous maps of disease rate estimates and the associated prediction variance. The methodology is illustrated using cholera and dysentery data collected in a cholera endemic area (Matlab) of Bangladesh.     

Protective effect of nordihydroguaiaretic acid (NDGA) against norgestrel induced genotoxic damage.

Nordihydroguaiaretic acid (NDGA) is a phenolic lignan and possesses antioxidant and number of properties potentially useful to man. The effect of NDGA was studied against norgestrel induced genotoxic damage, using sister chromatid exchanges (SCEs), chromosomal aberrations (CAs), mitotic index (MI) and replication index (RI) as parameters. Amounts of 5, 10 and 20 microM of norgestrel was tested for its genotoxic effect in the absence as well as presence of S9 mix, and was found to be genotoxic at 10 and 20 microM in the presence of S9 mix. Again, 10 microM of norgestrel was treated with 0.5 and 1 microM of NDGA, separately, in the presence of S9 mix. Similar treatment was given with 20 microM of norgestrel. Treatments given with NDGA result in the reduction of SCE, CA and increase of MI as well as RI, suggesting its protective action on human lymphocytes in vitro against the norgestrel induced genotoxic damage.     

Percutaneous treatmerit of heterogertous predorninantly solid echopattern echinococcal cysts of the liver

Purpose: We report our technique for and results of percutaneous treatment of heterogenous, predominantly solid echopattern hepatic hydatid cysts (HHC), i.e., complex type IV cysts according to Gharbi's sonographic classification of HHC. Methods: Eight patients with nine complex type IV HHC were treated by percutaneous aspiration followed by hypertonic saline ablation, using a 14 Fr van Sonnenberg sump drainage catheter under sonographic and fluoroscopic guidance. Results: Successful drainage of cysts contents was achieved in all eight patients. No major complications, such as anaphylaxis, abdominal dissemination, cyst recurrence, or death, occurred. Minor complications including pain (n = 4), mild fever (n = 5), right reactive pleural effusion (n = 4), and transient hypernatremia (n = 2) were observed and managed conservatively. Follow-up imaging studies for an average period of 15 months (range 1–48 months) showed either complete healing (n = 3) or significant reduction in the size of the cyst with solidification (n = 6). Conclusion: Nine complex type IV HHC were effectively treated by suction of the membranes and hypertonic saline ablation using a 14 Fr sump drainage catheter, without major complications.     

A novel biomarker for staging human prostate adenocarcinoma: overexpression of matriptase with concomitant loss of its inhibitor, hepatocyte growth factor activator inhibitor-1.

BACKGROUND: Matriptase, a type II transmembrane serine protease is involved in angiogenesis, degradation of extracellular matrix, and in the progression of some epithelial cancers. Here, we establish the clinical significance of matriptase and its inhibitor, hepatocyte growth factor activator inhibitor-1 (HAI-1), during the progression of human prostate cancer (CaP). METHODS: The expression patterns of matriptase and HAI-1 were determined in primary cultures of normal human prostate epithelial (NHPE) cells, human CaP cells LNCaP, DU-145, CWR22Rnu1, and PC-3, and in tissue samples of 172 patients with normal prostate, benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN), and adenocarcinoma of different tumor grades. RESULTS: The protein and mRNA levels of matriptase were significantly higher in all carcinoma cells as compared with NHPE cells. Conversely, all CaP cells exhibited a reduced expression of HAI-1 as compared with NHPE cells. A progressive increase in the protein levels of matriptase was observed with increasing tumor grade in CaP specimens as compared with normal and BPH tissue specimens. Tissue samples of normal prostate exhibited a high constitutive protein level of HAI-1 compared with BPH and low-grade cancer with a progressive loss with increasing tumor grade. CONCLUSION: The increased expression of matriptase and loss of HAI-1 may be an important event during the progression of CaP in humans. We suggest that the ratio of these two gene products may serve as a promising biomarker for CaP progression and a potential marker for establishing the efficacy of therapeutic and chemopreventive interventions.     

Botulinum toxin injection of the inferior oblique muscle for the treatment of superior oblique muscle palsy.

PURPOSE: To evaluate botulinum toxin injection of the inferior oblique muscle for management of superior oblique (SO) paresis. METHODS: We undertook a prospective case series of injections of the ipsilateral inferior oblique (IO) muscle with 10-20 units of botulinum toxin type A in patients with a SO muscle palsy/paresis of less than 2 years' duration. RESULTS: We enrolled 16 patients (18 eyes) with a mean age of 33.7 years. The median time from onset of symptoms until injection was 6 months. The cause of paresis was trauma for 81% of the patients. The mean hypertropia decreased from 6.4(Delta) to 1.9(Delta) at 6 months after treatment. Other clinical measures improved: mean IO overaction from + 1.7 to + 0.6, mean SO underaction from -1.5 to -0.4, mean subjective torsion from 9.3 degrees to 0.4 degrees , and mean head tilt from 8.4 degrees to 1.1 degrees. CONCLUSIONS: Botulinum toxin injection to IO muscle reduces the symptoms of SO paresis while patients are waiting for recovery.     

Corneal endothelial cell density and morphology in normal Iranian eyes

Background  

We describe corneal endothelial cell density and morphology in normal Iranian eyes and compare endothelial cell characteristics in the Iranian population with data available in the literature for American and Indian populations.     

Bcl-2 antisense oligonucleotides are effective against systemic but not central nervous system disease in severe combined immunodeficient mice bearing human t(14;18) follicular lymphoma.

The t(14;18) is present in 85-90% of follicular lymphomas. It results in overexpression of the Bcl-2 protein, which inhibits apoptosis and plays a role in lymphomagenesis. Bcl-2 antisense oligonucleotides (ODNs) down-regulate Bcl-2 expression and inhibit growth of the follicular lymphoma cell line WSU-FSCCL. In this study, we have established a human lymphoma xenograft model in severe combined immunodeficient (SCID) mice using the WSU-FSCCL cell line. s.c., i.v., or i.p. injection of WSU-FSCCL cells into SCID mice results in the development of disseminated tumors, with the liver, spleen, bone marrow, and lymph nodes as major sites of disease. Tumors were fatal in 7-14 weeks, depending on cell inoculum and route of administration. Immunohistochemistry, flow cytometry, and cytogenetic analysis confirmed the human B-cell origin of tumor cells in the xenograft. Phosphorothioate ODNs against the translation initiation site of bcl-2 mRNA in the antisense and mismatched antisense sequences were administered i.v. or i.p. to the xenograft models three times a week for 2 weeks, starting on day 7 after tumor injections. Antisense-treated animals had significantly longer survival (mean, 11.6 weeks) compared with 7.6 weeks for the control group and 7.5 weeks for the mismatched antisense-treated animals (P = 0.002 and 0.004, respectively). More significantly, a pathological examination showed no tumor in the liver, spleen, or bone marrow of the antisense group. However, subsequent experiments showed that the central nervous system was involved, causing mice to die although other sites were disease free. We conclude that bcl-2 antisense ODN therapy is effective against systemic FSCCL disease in SCID mice xenografts; however, it does not prevent disease dissemination into the central nervous system causing animal death.     

Molecular Cytogenetic Characterization of Drug-resistant Leukemia Cell Lines by Comparative Genomic Hybridization and Fluorescence in situ Hybridization

Resistance to chemotherapeutic drugs is one of the major difficulties encountered during cancer chemotherapy. To detect genomic aberrations underlying the acquired drug resistance, we examined three cultured human myelomonocytic leukemia cell sublines each resistant to adriamycin (ADR), 1-β–1- d -arabinofuranosylcytosine (ara-C), or vincristine (VCR), using comparative genomic hybridization (CGH), fluorescence in situ hybridization (FISH), RT-PCR, and western blot techniques. Chromosomes 7, 10 and 16 most conspicuously showed frequent aberrations among the resistant sublines as compared to the parental KY–821 cell line. In ADR-resistant cells, gains at 7q21, 16p12, 16p13.1–13.3, 16q11.1–q12.1, and losses at 7p22–pter, 7q36–qter, 10p12, 10p11.2–pter, 10q21–q25, 10q26–qter were notable. In ara-C-resistant cells, no remarkable gain or loss on chromosome 7, but losses at 10p14–pter, 10q26–qter and 16p11.2–p11.3 were observed. In VCR-resistant cells, gain at 7q21 and losses at 10p11–p13, 10p15 and 16p11.2–p13.3 were found. FISH identified amplified signals for the MDR–1 gene located at 7q21.1 in ADR-and VCR-but not ara-C-resistant cells, and for the MRP–1 gene located at 16pl3.1 in ADR-resistant cells. These findings were validated at the mRNA and protein levels. Overlapping of the amplified MRP–1 gene with MDR–1 gene may play a critical part in the acquisition of resistance to ADR. Resistance to ara-C excluded MDR–1 gene involvement and highlighted other key genes such as MXR gene. Several other genes putatively involved in the development of drug resistance might lie in other aberrated chromosomal regions.